Musculoskeletal diseases, injuries and disorders are the most common health complaint in the Unites States. Indeed, 1 in 2 women and 1 in 5 men over the age of 50 will suffer a bone fracture in their remaining lifetime. These fractures are associated with significant morbidity and increased mortality. The current approach for assessing skeletal fragility is measurement of bone mineral density (BMD) by DXA (dual-energy x-ray absorptiometry). However, less than half of those who suffer fractures have BMD values in the osteoporotic range, providing strong rationale for investigating other determinants of bone strength. Thus, novel techniques capable of measuring bone microstructure in vivo, such as the one requested in this application, are needed to shift the paradigm beyond BMD and provide an improved understanding of the factors that contribute to skeletal fragility. This proposal requests funds to purchase a second-generation high-resolution peripheral computed tomography device (XtremeCTII) which allows in vivo, non-invasive 3D assessment of bone density and microarchitecture at peripheral skeletal sites in both children and adults. These measurements are a critical advantage over traditional 2D-based BMD measurements. Further, this state-of-the-art XtremeCTII system represents a major technological advance compared to the first generation device in that it provides for a significant improvement in image resolution, a re-designed gantry that allows more proximal measurements (even up to the knee and elbow), and a much faster scan time. These technologic advances will provide improved ability to detect skeletal abnormalities and monitor longitudinal changes in bone microstructure. Availability of this new device will enhance the research of 16 major and minor users with 15 NIH-funded grants. We have successfully operated an HR-pQCT Imaging Core facility for the past 9 years, and thus have the experience and expertise to continue to provide this service in an efficient and cost-effective manner. The institution (MGH) has committed key financial support for necessary renovations and ongoing service & maintenance costs of the device, as has agreed to financially support the instrument for its useful life should there be a shortfall in funding. In sum, this equipment will fill a critical need for NIH-funded investigators from MGH and surrounding institutions to perform investigations into the mechanisms underlying skeletal fragility in persons of all ages.